Neferine Potentiates the Antitumor Effect of Cisplatin in Human Lung Adenocarcinoma Cells via a Mitochondria-mediated Apoptosis Pathway.

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Neferine Potentiates the Antitumor Effect of Cisplatin in Human Lung Adenocarcinoma Cells via a Mitochondria-mediated Apoptosis Pathway.

J Cell Biochem. 2017 Feb 18;:

Authors: Sivalingam KS, Paramasivan P, Weng CF, Vijaya Padma V

Abstract
Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G0/G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome C, p53 levels, then activated cleavage forms of caspase-9, caspase-3 and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. This article is protected by copyright. All rights reserved.

PMID: 28214344 [PubMed - as supplied by publisher]

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